DESCRIPTION (adapted from application, page 328): The purpose of this proposal is to demonstrate that key hypotheses related to the natural history of HIV-infected women in the era of potent therapy can be best addressed through continued follow up of individuals enrolled in the Women's Interagency HIV Study (WIHS). Established in 1993 to study HIV disease among women in the U.S., the WIHS has assembled an experienced research network and an extensive infrastructure that serves as a platform for cutting-edge laboratory and clinical science. Participants encompass a traditionally understudied population, yet WIHS has developed effective strategies to successfully maintain retention and follow up, thus ensuring their long-term characterization and the ascertainment of outcomes. To capitalize upon the comprehensive data collected at regularly scheduled visits, state-of-the art analytical approaches have been implemented to assess the association of factors collected prior to and after therapy initiation with a broad spectrum of beneficial and adverse outcomes. In addition to testing important hypotheses as part of the core WIHS study, we have created a research platform of data and specimens that constitutes an important tool for current and future studies. This platform permits investigators inside and outside the WIHS community to use longitudinally collected data and specimens to test new hypotheses, and thus avoid the costs of compiling needed resource de novo. The study has been highly collaborative, sharing data and specimens with a multitude of investigators funded through investigator-initiated studies (R01s and other mechanisms) and in supporting new clinical scientists via WIHS linked early career development awards. Each of these elements has contributed to continued productivity, with some 320 publications as of this submission. The scientific and operational components of the WIHS are complex and dynamic. Part A of this application will describe the cohort and key scientific achievements that have occurred since our previous submission in March 2002;a presentation of our scientific and organizational structure;and our proposed scientific hypotheses and a research agenda for 2007-2012 that has been organized into four interrelated research projects and six cores.